Soft tissue defects resulting from trauma, chronic diseases, congenital anomalies, aging or tumor resection often require implant technologies to restore the contour and symmetry of native tissue. For example, breast cancer patients suffer from loss of breast tissue after lumpectomy or mastectomy and are dependent on autologous tissue grafts or implant materials to restore the appearance of the breast mound. Adipose tissue engineering may provide an alternative by using progenitor cells, biomaterials, and bioactive molecules for the regeneration of biologically viable and remodeling-capable tissues for the repair of the breast contour and symmetry. But current synthetic or graft implant technologies suffer from common complications such as limited cell and tissue source, donor site morbidity, allergic reactions, foreign body reactions, rapid resorption and necrosis (see e.g., Flassbeck et al. (2003); Wong et al. (2006); Mizuno et al. (2005); Goodwin et al. (2005)).
Various autologous replacement or implant technologies have been previously developed. Autologous grafts have the advantage of using the patient's own tissue, and there is no need to test for allergic reaction. But autologous grafts and fillers may not be permanent, and volume reduction will occur over time. As with all procedures involving autologous tissue, donor site morbidity includes trauma and scarring. This is apparent in the reconstruction of larger defects, such as breast reconstruction for women after tumor resection. Furthermore, there may be a lack of appropriate donor site. For example, a very thin woman may not have the extra skin and adipose tissue in the abdomen or buttocks to act as donor tissue for breast reconstruction. Such patients can only be treated with artificial implants.
Breast implants have been used for many decades as prosthesis for augmentation, reconstruction (after mastectomy) or correction of the abnormalities that affect the shape and size of the breast (for review, see generally Van and Heymans (2004)). Approximately 300,000 women receive silicone breast implants every year in the United States alone, according to the American Society for Aesthetic Plastic Surgery (ASAPS) and The American Society of Plastic Surgeons (ASPS). The two primary types of synthetic breast implants are saline filled and silicone gel filled implants. Silicone implants have a silicone shell filled with viscous silicone gel whereas saline implants have a silicone elastomer shell filled with sterile saline liquid. Problems associated with synthetic breast implants include deflation, capsular contracture, infection, shifting, and calcium deposits. Other filler materials such as polyvinyl alcohol and hyaluronic acid have been introduced, however never progressed beyond experimental stages in the United States (Van and Heymans (2004)). Synthetic breast implants are typically not lifetime devices, and breast implantation is likely not a one-time surgery according to the Food and Drug Administration (FDA).
Mastectomy results in loss of the entire breast and reconstruction is necessary to restore natural body contour. The mainstay of non-autologous reconstruction involves the use of implants with or without skin expansion and autologous fat grafts (Alper (2000); Shenaq and Yuksel (2002)). However, recent advances made in synthetic and non-synthetic (autologous) approaches for breast mound reconstruction still yield suboptimal results. Current techniques for autologous breast reconstruction include the transverse rectus abdominis myocutaneous (TRAM) flap, and latissimus dorsi flap with or without alloplastic implants. Recently, free tissue transfer techniques have allowed the use of more sophisticated perforator flaps, which harvests skin and subcutaneous fat while sacrificing the underlying muscles. Examples include the deep inferior epigastric perforator (DIEP) flap and superior gluteal perforator flap (SGAP) (Arnez et al. (1999a, b)). But these procedures have significant limitations, including donor-site morbidity and limitations on the size of the reconstructed breasts. Moreover, autologous adipose tissue results in 50-70% graft volume reduction due to resorption (Niechajev and Sevcuk (1994); Matsudo and Toledo (1988); de la Fuente and Tavora (1988); Chajchir and Benzaquen (1986)). Balancing procedures such as augmentation, mastopexy (breast lift) or breast reduction are frequently necessary to restore symmetry.
Ideally, implant material should be easy to obtain, durable, non-immunogenic and biocompatible with the human body, easy to shape, able to be incorporated, and minimize donor site morbidity.
Thus there is the need for better implants that are durable, biocompatible, look and feel similar to natural breast tissue, and capable of maintaining shape and dimensions in the long term. Moreover, the implants should not obscure screening examinations and imaging studies in the detection of breast cancer (Brown et al. (2004)).
Soft tissue defects resulting from trauma, chronic diseases, congenital anomalies, aging or tumor resection often require implant technologies to restore the contour and symmetry of native tissue. Breast cancer patients suffer from loss of breast tissue after lumpectomy or mastectomy and are primarily dependent on implant materials to restore the appearance of the breast mound. Adipose tissue engineering provides tools including progenitor cells, biomaterials, and bioactive molecules for the regeneration of live, remodeling, bioactive tissues for the repair of the breast contour and symmetry.
Current technologies deliver synthetic materials that are foreign bodies such as silicone and saline implants. Autologous tissues are not used regularly due to lack of donor tissue, scarring, prolonged hospitalization, implant necrosis.
Current synthetic or graft implant technologies suffer from common complications such as limited cell and tissue source, donor site morbidity, allergic reactions, foreign body reactions, rapid resorption and necrosis.
Approximately 300,000 women receive silicone breast implants every year in the United States alone, according to the American Society for Aesthetic Plastic Surgery (ASAPS) and The American Society of Plastic Surgeons (ASPS), and breast surgical procedures costs add up to nearly $1.5 billion dollars a year. Recent enabling technologies using stem cells have shown the potential to revolutionize medical treatment including the methods of reconstruction of breast tissues post lumpectomy (partial removal of breast tissue) or mastectomy (complete resection of the breast). The present invention provides methods and compositions toward that goal.